We will continue our studies on adaptive synaptic growth using the hippocampal formation as a model system. Our previous studies have shown that partial denervation causes an extensive reorganization of hippocampal circuitry over the course of a few days. We will continue to examine the cellular and molecular events of reinnervation in the hippocampus. We will explore the manner in which hippocampal circuitry responds to loss of intrinsic cell groups and the way in which tissue implants grow in the reorganized hippocampus. The growth pattern of fibers from implants should indicate whether the hippocampus has become respecified in a way that is consistent with a change in the chemoaffinity of the target cells. Our molecular studies will focus on the structure and molecular properties of synaptic junctions. We will continue to examine the components of mature synaptic junctions, we will begin to study the assembly of synaptic junctions in vivo during development, and we will seek to re-constitute synaptic junctions from isolated components in vitro. To complement the above studies, we propose to establish primary cultures of hippocampal neurons. This will provide a system more accessible to experimental manipulation.